Search

Background Pepper from Capsicum species is a well-established spice with a rich history of culinary use. Some observations have linked its consumption to gastrointestinal discomfort and alterations in stool patterns while it is considered beneficial in some cultures. However, there is lack of information on the direct effect of pepper consumption on human gut microbiota, we conducted dietary intervention studies to assess the impact of pepper on gut bacteriome composition in humans. Methods Ten healthy volunteers were recruited, and each person received 200 ml of 0.14 g/ml fresh Habanero Pepper (Capsicum chinense) daily over a 4-day period after which they abstained from pepper consumption for the subsequent 4 days before resumption of their normal diet. Stool samples were collected at baseline, after pepper consumption, after 4 days without pepper and after 4- and 6-days resumption of normal diet. We sequenced the V3-V4 region of the 16S rRNA gene and analyzed microbial diversity and composition using the QIIME2 pipeline and relevant R packages. Results Consumption of pepper over a 4-day period led to a higher abundance of Verrucomicrobia, a phylum rarely found in significant proportions at other time points. There was a gradual depletion of Shigella and Staphylococcus spp. from baseline untill the end of the study. Other taxa showed timepoint specific associations, emphasizing the potential impact of short-term dietary interventions on the relative abundance of these genera. Conclusions Our study adds nuance to the understanding of diet-microbiota interactions, highlighting the intricate relationship between pepper consumption and gut bacteriome composition. Further exploration of these dynamics holds promise for personalized dietary recommendations and targeted interventions to support gut microbial health.

Background: Pepper from Capsicum species is a well-established spice with a rich history of culinary use. Some observations have linked its consumption to gastrointestinal discomfort and alterations in stool patterns while it is considered beneficial in some cultures. However, there is lack of information on the direct effect of pepper consumption on human gut microbiota, we conducted dietary intervention studies to assess the impact of pepper on gut bacteriome composition in humans. Methods: Ten healthy volunteers were recruited, and each person received 200 ml of 0.14 g/ml fresh Habanero Pepper (Capsicum chinense) daily over a 4-day period after which they abstained from pepper consumption for the subsequent 4 days before resumption of their normal diet. Stool samples were collected at baseline, after pepper consumption, after 4 days without pepper and after 4- and 6-days resumption of normal diet. We sequenced the V3-V4 region of the 16S rRNA gene and analyzed microbial diversity and composition using the QIIME2 pipeline and relevant R packages. Results: Consumption of pepper over a 4-day period led to a higher abundance of Verrucomicrobia, a phylum rarely found in significant proportions at other time points. There was a gradual depletion of Shigella and Staphylococcus spp. from baseline untill the end of the study. Other taxa showed timepoint specific associations, emphasizing the potential impact of short-term dietary interventions on the relative abundance of these genera. Conclusions: Our study adds nuance to the understanding of diet-microbiota interactions, highlighting the intricate relationship between pepper consumption and gut bacteriome composition. Further exploration of these dynamics holds promise for personalized dietary recommendations and targeted interventions to support gut microbial health. [ABSTRACT FROM AUTHOR]

This paper presents an analysis of off board bidirectional Plug in Electric Vehicle (PEV) Charger. Since, normally, the control command for such chargers are given in terms of desired real and reactive power, a model of the system is formulated directly in terms of these variables. A detailed steady state analysis of the system is presented for the entire possible range of operation and for a given battery state of charge (SOC) rather than selecting points of operation a priori. This result shows the various possibilities of the system and informs further structural studies of the system and the design of controllers to meet the desired control objectives. [ABSTRACT FROM AUTHOR]

Objectives: This study investigated the implementation of the ABCDEF bundle and the factors associated with its implementation according to national income levels., Methods: This study is cross-sectional research. We conducted a secondary analysis of an international 1-day point-prevalence study that investigated the implementation of the ABCDEF bundle in critically ill patients. All patients admitted to the ICU were eligible. This study was conducted across 135 ICUs in 54 countries, including data from 664 patients. Outcomes were categorized according to the income level of the country (high-income, middle-income, and low-income countries) in which each ICU was located. A multilevel generalized linear model was developed to identify the factors associated with ABCDEF bundle implementation for each income level., Results: We identified 664 patients in 79 high-income countries, 278 in 26 middle-income countries, and 287 in 30 low-income countries ICUs. Implementation rates of the ABCDEF bundle were low for all income levels but varied. Few individuals completed the entire bundle on the survey date. Common factors associated with the implementation among all income levels were a multidisciplinary team approach for Element A (pain) and mechanical ventilation use for Element C (sedation), which were also associated with lower Element E (mobility). The existence of a protocol was frequently identified as a promoting factor associated with ABCDEF bundle implementation. The associated factors varied by income level; for example, dedicated intensivists were only identified in high-income countries, but not in middle-income countries or low-income countries., Conclusions: The overall low ABCDEF bundle implementation rates necessitate action. As factors associated with its implementation vary according to national income level, tailored strategies are essential for improving ICU care quality., Trial Registration: NA., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2025.)

Background Fatigue presents an important challenge for patients discharged from intensive care units (ICUs). Despite its importance, data on the prevalence and clinical impact of post-ICU fatigue remain limited. In particular, the proportion of patients in clinical settings in Japan who find fatigue distressing, as well as the associations between fatigue, risk factors, and self-rated health, have not been fully explored using validated fatigue measures. Therefore, this study aimed to assess the prevalence of fatigue, identify its associated risk factors, and examine the relationship between fatigue and self-rated health status six months after ICU discharge in Japan. Methods This single-center, ambidirectional cohort study administered a survey to patients aged ≥18 years, six months after ICU discharge, to assess fatigue and self-rated health. Retrospective data were also collected from patients' medical records during hospitalization. Fatigue prevalence was the primary endpoint, measured using the cutoff value of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale. Logistic regression analysis was performed to identify risk factors for fatigue. Locally weighted scatterplot smoothing (LOWESS) plots were generated with FACIT-F scale scores, and the association between fatigue and EuroQol 5 Dimensions 5-Level Visual Analog Scale (EQ-VAS) was analyzed. Results Questionnaires were sent to 87 patients, of whom 81 (93.1%) responded. Eight patients (9.9%) with missing FACIT-F scores were excluded, leaving 73 patients for analysis. The median (interquartile range) age of eligible patients was 74 (63-81) years, and 33 patients (45%) were male. Forty-six patients (63%) reported fatigue. Multivariate analysis identified a higher body mass index (BMI) at ICU admission as an independent risk factor for fatigue (odds ratio (OR) = 1.195; 95% confidence interval (CI) 1.018-1.447; p < 0.05). EQ-VAS scores were significantly lower in the fatigue group (OR 72.5, 95% CI 60-83.8 vs. OR 90, 95% CI 80-90; p < 0.01). Conclusion This study found that many patients in Japanese ICUs experience fatigue, even when disease severity is low. Additionally, BMI at ICU admission was identified as an independent risk factor for fatigue six months after ICU discharge. Regular follow-up on fatigue after ICU discharge is essential for improving long-term outcomes., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Ethics Review Board of the Graduate School of Nursing at Sapporo City University issued approval No. 10. This study was approved by the Ethics Review Board of the Graduate School of Nursing at Sapporo City University (10 2023-10-13, Central IRB) and the Hospital Director of Sapporo Medical University Hospital (352-125 2023-10-23). Study period: October 23, 2023, to March 31, 2024. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2025, Niiyama et al.)

Oral hygiene care is important for ventilator-associated pneumonia prevention. However, the optimal oral hygiene care approach remains unclear. A network meta-analysis was conducted to compare the efficacy of various oral hygiene care methods for ventilator-associated pneumonia prevention in critically ill patients, and the methods were ranked. A literature search of three representative databases was conducted. We only analyzed parallel randomized controlled trials conducted to analyze the use antiseptics or toothbrushes in oral hygiene care for adult patients undergoing invasive mechanical ventilation in the intensive care unit. The outcome measure was the incidence of ventilator-associated pneumonia. Bias risk was assessed using the Cochrane Risk of Bias 2 tool, and the confidence in the evidence was evaluated using the CINeMA approach. Statistical analyses were performed using R 4.2.0., GeMTC package, and JAGS 4.3.1. The review protocol was registered in PROSPERO (registration number: CRD42022333270). Thirteen randomized controlled trials were included in the qualitative synthesis and twelve randomized controlled trials (2395 participants) were included in the network meta-analysis. Over 50% of the included studies were conducted in medical-surgical intensive care units. Ten treatments were analyzed and 12 pairwise comparisons were conducted in the 12 included studies. Analysis using surface under the cumulative ranking curves revealed that brushing combined with chlorhexidine 0.12% was most likely the optimal intervention for preventing ventilator-associated pneumonia (88.4%), followed by the use of chlorhexidine 0.12% alone (76.1%), and brushing alone (73.2%). Oral hygiene care methods that included brushing had high rankings. In conclusion, brushing combined with chlorhexidine 0.12% may be an effective intervention for preventing ventilator-associated pneumonia in critically ill patients. Furthermore, brushing may be the optimal oral hygiene care method for preventing ventilator-associated pneumonia in the intensive care unit. Further research is needed to verify these findings as the CINeMA confidence rate was low for each comparison., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yamakita et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background This study aims to develop and validate a comprehensive prediction model for ICU readmissions. Readmission following ICU discharge is associated with adverse outcomes such as increased mortality, prolonged hospital stays, and elevated healthcare costs. Consequently, predicting and preventing readmissions is crucial. Previous models for predicting ICU readmissions were primarily based on physiological indices; however, these indices fail to capture the complete nature of treatment or patient conditions beyond physiological measures, thereby limiting the accuracy of these predictions. Methodology A total of 1,400 patients who had an unplanned ICU admission at Sapporo Medical University Hospital from January 2015 to October 2022 were included; a single regression analysis was performed using unplanned ICU readmission as the dependent variable. After performing a single regression analysis, logistic regression analysis using the stepwise method was performed using variables with significant differences, and a predictive nomogram was created using the variables that remained in the final model. To internally validate the predictive nomogram model, nonparametric bootstrapping (1,000 replications) was performed on the original model. Results Of the 1,400 patients who had an unplanned admission to the ICU, 114 (8.1%) were readmitted to the ICU unplanned. Seven main variables (Sequential Organ Failure Assessment score, respiratory rate, Glasgow Coma Scale, sleep disturbance, Continuous Kidney Replacement Therapy, presence of tracheal suctioning, and Oxygen Saturation) were selected to be associated with ICU readmission. The evaluation of the models showed excellent discrimination with an area under the receiver operating characteristic of 0.805 (original model) and 0.796 (bootstrap model). Calibration plots also confirmed good agreement between observed and predicted reentry. Conclusions This new predictive model is more accurate than previous models because it includes physiological indicators as well as other patient conditions and procedures needed and is expected to be used in clinical practice. In particular, the inclusion of new factors, such as sleep disturbance and the need for tracheal suctioning, enabled a more comprehensive patient assessment. The use of this predictive nomogram as a criterion for discharging ICU patients may prevent unplanned ICU readmission., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. The Institutional Review Board of Sapporo Medical University issued approval 342-157, December 1, 2022. Owing to the observational nature of this study, the information was released on an opt-out basis. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Nakano et al.)

Families of critically ill patients are predisposed to tremendous burdens when their relatives are admitted to the intensive care unit (ICU). Postintensive care syndrome family (PICS-F) can be described as a devastated life, encompassing psychological, physical, and socioeconomical burdens that begin with the emotional impact experienced by the family when the patient is admitted to the ICU. PICS-F was primarily proposed as a clinically significant psychological impairment, but it needs to be extended beyond the psychological impairment of the family to include physical and socioeconomical impairments in the future. The prevalence of physiological problems including depression, anxiety and post-traumatic syndrome is 20-40%, and that of non-physiological problems including fatigue is 15% at 6 months after the ICU stay. Assessment of PICS-F was frequently conducted at 3- or 6-month points, although the beginning of the evaluation was based on different assessment points among each of the studies. Families of ICU patients need to be given and understand accurate information, such as the patient's diagnosis, planned care, and prognosis. Prevention of PICS-F requires a continuous bundle of multifaceted and/or multidisciplinary interventions including providing a family information leaflet, ICU diary, communication facilitators, supportive grief care, and follow-up, for the patient and families from during the ICU stay to after discharge from the ICU. This is the first comprehensive review of PICS-F to address the concept, risk factors, assessment tools, prevalence, and management to prevent PICS-F to facilitate acute care physicians' understanding of PICS-F., Competing Interests: Nobuyuki Nosaka is working on the research about PICS‐F under funding from SHARP CORPORATION, but he has not received any direct support for the manuscript. Nobuyuki Nosaka is also working on the research about PICS and PICS‐F under funding from LIXIL Corporation, but he has not received any direct support for the manuscript. The remaining authors have disclosed that they do not have any potential conflicts of interest., (© 2024 The Authors. Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine.)

Introduction Work-life balance (WLB) is a critical concern for emergency medical technicians (EMTs) because it significantly affects the provision of comprehensive emergency medical services (EMS). This study investigated personal and work-related factors influencing work-to-family negative spillover (WFNS), a key element of WLB, among EMTs. Methods A web-based survey was conducted from July 26 to September 13, 2021, among EMTs in Hokkaido, Japan. The study included 21 facilities that were randomly selected from 42 fire stations. The Japanese version of the Survey Work-Home Interaction-NijmeGen (SWING-J) was used to measure WFNS. Personal background factors, such as age, sex, years of work experience, and education, were surveyed. We also evaluated work environment factors, such as weekly working hours, monthly night shifts, monthly overtime hours, and yearly paid vacation days. Unpaired Student's t-tests, one-way analysis of variance (ANOVA), and multilevel generalized linear model (MGLM) analyses were used to explore the relationships between WFNS and personal and work-related factors. Results A total of 912 respondents were included in our analysis. They were predominantly male (98.2%), with an average EMT work experience of 12.7 years and a mean WFNS score of 1.16 (standard deviation (SD) = 1.67). MGLM analysis, adjusting for covariates, identified years of work experience (β = -0.129, p = 0.001), monthly overtime hours (β = 0.184, p < 0.001), and yearly paid vacation days (β = -0.170, p < 0.001) as independent factors associated with WFNS. Conclusion This study suggested that adjusting WFNS among EMTs could be achieved by reducing overtime hours and fostering an organized approach to paid leave within the work environment., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Haruna et al.)

Background: The assessment of post-intensive care syndrome (PICS) is challenging due to the numerous types of instruments. We herein attempted to identify and propose recommendations for instruments to assess PICS in intensive care unit (ICU) survivors., Methods: We conducted a scoping review to identify PICS follow-up studies at and after hospital discharge between 2014 and 2022. Assessment instruments used more than two times were included in the modified Delphi consensus process. A modified Delphi meeting was conducted three times by the PICS committee of the Japanese Society of Intensive Care Medicine, and each score was rated as not important (score: 1-3), important, but not critical (4-6), and critical (7-9). We included instruments with ≥ 70% of respondents rating critical and ≤ 15% of respondents rating not important., Results: In total, 6972 records were identified in this scoping review, and 754 studies were included in the analysis. After data extraction, 107 PICS assessment instruments were identified. The modified Delphi meeting reached 20 PICS assessment instrument recommendations: (1) in the physical domain: the 6-min walk test, MRC score, and grip strength, (2) in cognition: MoCA, MMSE, and SMQ, (3) in mental health: HADS, IES-R, and PHQ-9, (4) in the activities of daily living: the Barthel Index, IADL, and FIM, (5) in quality of life: SF-36, SF-12, EQ-5D-5L, 3L, and VAS (6), in sleep and pain: PSQI and Brief Pain Inventory, respectively, and (7) in the PICS-family domain: SF-36, HADS, and IES-R., Conclusion: Based on a scoping review and the modified Delphi method, 20 PICS assessment instruments are recommended to assess physical, cognitive, mental health, activities of daily living, quality of life, sleep, and pain in ICU survivors and their families., (© 2023. The Author(s).)

Objective: Burnout among emergency medical technicians is a serious problem affecting delivery of quality emergency medical services. Although the repetitive nature of the job and lower education level requirements for technicians have been reported as risk factors, little is known about the influence of burden of responsibility, degree of supervisor support, and home environment on burnout among emergency medical technicians. This study aimed to test the hypothesis that burden of responsibility, degree of supervisor support, and home environment increase burnout probability., Methods: A web-based survey was conducted among emergency medical technicians in Hokkaido, Japan from July 26, 2021 to September 13, 2021. A total of 21 facilities were randomly selected from 42 fire stations. Prevalence of burnout was measured using the Maslach Burnout-Human Services Survey Inventory (MBI-HSS). Burden of responsibility was measured using a visual analog scale. Occupational background was also measured. Supervisor support was measured using the Brief Job Stress Questionnaire (BJSQ). Family-work negative spillover was measured using the Japanese version of Survey Work-Home Interaction-NijmeGen (SWING). The cutoff value for burnout syndrome was defined as emotional exhaustion≥27 and/or depersonalization≥10., Results: A total of 700 survey respondents were included, and 27 surveys with missing data were excluded. The suspected burnout frequency was 25.6%. Covariates were adjusted using multilevel logistic regression model analysis. Low supervisor support (odds ratio, 1.421; 95% confidence interval, 1.136-1.406; P<0.001) and high family-work negative spillover (odds ratio, 1.264; 95% confidence interval, 1.285-1.571; P<0.001) were independent factors associated with higher probability of burnout., Conclusion: This study indicated that focusing on improvement of supervisor support for emergency medical technicians and creating supportive home environments may assist in reducing burnout frequency.

The purpose of this study was to develop and validate an emergency medical technician (EMT) care patient satisfaction scale to measure patient satisfaction with prehospital emergency care. To date, patient satisfaction surveys of EMTs have been performed subjectively, e using each facility's questionnaire, without the use of a validated patient satisfaction scale. However, no specific scale has been devised to assess patient satisfaction with EMTs. The study population comprised patients who used an ambulance between November 2020 and May 2021 (N = 202). A survey instrument was administered to participants who provided informed consent. In the process of validating the patient satisfaction scale, an exploratory factor analysis (EFA) of construct validity was performed. The results of the EFA showed a factor structure consisting of five factors: "teamwork", "explanation and communication", "physical treatment and psychological support", "quickness of transport", and "environment in the ambulance". In addition, domain and summary scores showed good internal reliability (Cronbach's range = 0.82-0.94). The patient satisfaction scale developed in this study was designed and validated considering the role of EMTs and patients' needs for prehospital care. This scale may be useful in the development of assessments and interventions to improve patient satisfaction with EMTs., Competing Interests: Conflict of interest: The authors declare no conflict of interest., (© 2023 the Author(s), licensee AIMS Press.)

Objectives: A clear development process and scientifically validated clinical practice competencies in standard critical care nursing (SCCN) have not yet been developed in Japan. Thus, this study aimed to develop a consensus-based set of SCCN competencies to provide a framework for critical care nursing education, training and evaluation., Design: Multistep, modified Delphi study (a systematic review, focus group interviews, a three-round web-based Delphi survey and an external validation process)., Participants: A systematic review of 23 studies, focus group interviews by 12 experts, a Delphi survey by 239 critical care experts (physicians, nurses and physical therapists) and an external validation by 5 experts (physicians and nurses)., Results: A systematic review identified 685 unique competencies. The focus group interviews resulted in the addition of 3 performance indicator items, a synthesis of 2 subdomains and 10 elements. Of the 239 participants, 218 (91.2%), 209 (98.9%) and 201 (96.2%) responded in rounds 1, 2 and 3 of the Delphi survey, respectively. After round 3, 57 items were below the consensus level and were removed in the final round. External validation process feedback was received from experts after two revisions to ensure that the final competencies were valid, applicable, useful and clear. The final set of competencies was classified into 6 domains, 26 subdomains, 99 elements and 525 performance indicators., Conclusions: This study found a set of SCCN competencies after a multistep, modified Delphi study. The results of this study are robust, and the competency framework can be used in multiple areas to improve clinical practice, including the assessment, training and certification of standard critical care nurses., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Appetite loss, a common but serious issue in older patients, is an independent risk factor for sarcopenia, which is associated with high mortality. However, few studies have explored the phenomenon of appetite loss after discharge from the intensive care unit (ICU). Therefore, we aimed to describe the prevalence of appetite loss and relationship between appetite loss and depression in patients living at home 12 months after intensive care. This study involved secondary analysis of data obtained from a published ambidirectional study examining post-intensive care syndrome 12 months after discharge (SMAP-HoPe study) conducted in 12 ICUs in Japan. We included patients aged > 65 years. The Short Nutritional Assessment Questionnaire and Hospital Anxiety Depression Scale were used for the analysis. Descriptive statistics and a multilevel generalized linear model were used to clarify the relationship between appetite loss and depression. Data from 468 patients were analyzed. The prevalence of appetite loss was 25.4% (95% confidence interval [CI], 21.5-29.4). High severity of depression was associated with a high probability of appetite loss (odds ratio, 1.2; 95%CI, 1.14-1.28; p = 0.00). Poor appetite is common 12 months after intensive care and is associated with the severity of depression., (© 2023. The Author(s).)

Background and Objectives: The main objective of a transitional care program (TCP) is to detect patients with early deterioration following intensive care unit (ICU) discharge in order to reduce unplanned ICU readmissions. Consensus on the effectiveness of TCPs in preventing unscheduled ICU readmissions remains lacking. In this case study assessing the effectiveness of TCP, we focused on the association of unplanned ICU readmission with high nursing activities scores (NASs), which are considered a risk factor for ICU readmission. Materials and Methods: This retrospective observational study analyzed the data of patients admitted to a single-center ICU between January 2016 and December 2019, with an NAS of >53 points at ICU discharge. The following data were extracted: patient characteristics, ICU treatment, acute physiology and chronic health evaluation II (APACHE II) score at ICU admission, Charlson comorbidity index (CCI), 28-day mortality rate, and ICU readmission rate. The primary outcome was the association between unplanned ICU readmissions and the use of a TCP. The propensity score (PS) was calculated using the following variables: age, sex, APACHE II score, and CCI. Subsequently, logistic regression analysis was performed using the PS to evaluate the outcomes. Results: A total of 143 patients were included in this study, of which 87 (60.8%) participated in a TCP. Respiratory failure was the most common cause of unplanned ICU readmission. The unplanned ICU readmission rate was significantly lower in the TCP group. In the logistic regression model, TCP (odds ratio, 5.15; 95% confidence interval, 1.46−18.2; p = 0.01) was independently associated with unplanned ICU readmission. Conclusions: TCP intervention with a focus on patients with a high NAS (>53 points) may prevent unplanned ICU readmission.

This study aimed to evaluate the effectiveness of nurse-led interventions for the prevention of mental health disorders after intensive care unit discharge through a systematic review of the literature. The searches were conducted in the MEDLINE (via PubMed), CINAHL, PsycINFO, and Cochrane Library databases for studies pertaining to such interventions. Two independent reviewers analyzed the studies, extracted data, and assessed the quality of the evidence. Six eligible articles were identified, all of which were regarding post-traumatic stress disorder after intensive care unit discharge. Some of the interventions were conducted during the admission and some after the discharge. One study found that multimedia education during admission improved anxiety and depression one week after discharge. The remaining five studies concluded that nurse-led interventions did not prevent mental health disorders three months to one year after intensive care unit discharge. Our review revealed a paucity of research into the effectiveness of nurse-led interventions for the prevention of mental health disorders after intensive care unit discharge. The timing and the content of these interventions, and the adequate training of nurses, appear to be key factors. Therefore, multidisciplinary interventions are likely to be more effective than those led by nurses alone.

This study evaluated the accuracy of predicting unplanned the intensive care unit (ICU) readmission using the Nursing Activities Score (NAS) at ICU discharge based on nursing workloads, and compared it to the accuracy of the prediction made using the Stability and Workload Index for Transfer (SWIFT) score. Patients admitted to the ICU of Sapporo Medical University Hospital between April 2014 and December 2017 were included, and unplanned ICU readmissions were retrospectively evaluated using the SWIFT score and the NAS. Patient characteristics, such as age, sex, the Charlson Comorbidity Index, and sequential organ failure assessment score at ICU admission, were used as covariates, and logistic regression analysis was performed to calculate the odds ratios for the SWIFT score and NAS. Among 599 patients, 58 (9.7%) were unexpectedly readmitted to the ICU. The area under the receiver operating characteristic curve of NAS (0.78) was higher than that of the SWIFT score (0.68), and cutoff values were 21 for the SWIFT and 53 for the NAS. Multivariate analysis showed that the NAS was an independent predictor of unplanned ICU readmission. The NAS was superior to the SWIFT in predicting unplanned ICU readmission. NAS may be an adjunctive tool to predict unplanned ICU readmission., Competing Interests: The authors declare no conflict of interest.

Background: Returning to work is a serious issue that affects patients who are discharged from the intensive care unit (ICU). This study aimed to clarify the employment status and the perceived household financial status of ICU patients 12 months following ICU discharge. Additionally, we evaluated whether there exists an association between depressive symptoms and subsequent unemployment status., Methods: This study was a subgroup analysis of the published Survey of Multicenter Assessment with Postal questionnaire for Post-Intensive Care Syndrome for Home Living Patients (the SMAP-HoPe study) in Japan. Eligible patients were those who were employed before ICU admission, stayed in the ICU for at least three nights between October 2019 and July 2020, and lived at home for 12 months after discharge. We assessed the employment status, subjective cognitive functions, household financial status, Hospital Anxiety and Depression Scale, and EuroQOL-5 dimensions of physical function at 12 months following intensive care., Results: This study included 328 patients, with a median age of 64 (interquartile range [IQR], 52-72) years. Of these, 79 (24%) were unemployed 12 months after ICU discharge. The number of patients who reported worsened financial status was significantly higher in the unemployed group (p<0.01) than in the employed group. Multivariable analysis showed that higher age (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.03-1.08]) and greater severity of depressive symptoms (OR, 1.13 [95% CI, 1.05-1.23]) were independent factors for unemployment status at 12 months after ICU discharge., Conclusions: We found that 24.1% of our patients who had been employed prior to ICU admission were subsequently unemployed following ICU discharge and that depressive symptoms were associated with unemployment status. The government and the local municipalities should provide medical and financial support to such patients. Additionally, community and workplace support for such patients are warranted., Competing Interests: The authors have declared that no competing interests exist.

This study aimed to develop and validate an emergency nursing-care patient satisfaction scale to measure patient satisfaction with emergency room (ER) nursing. Patient satisfaction scales for ER nursing have been validated without considering the perspectives of the healthcare system or cultural background of the country. Moreover, although nursing care is changing with COVID-19, no scale has been specifically designed to assess patient satisfaction with ER nursing. The study population included patients who visited five ERs in Japan (March to December 2021) ( n = 135). The rating scales were provided to patients who visited the ER and gave consent, and the patients were asked to reply. In the process of validating the scale, exploratory and confirmatory factor analyses of the construct and criterion validity were conducted. The confirmatory factor analysis results showed a factorial structure consisting of four factors. The domain and summary scores demonstrated good-to-excellent internal reliability (Cronbach's range = 0.81-0.89). This patient satisfaction scale was designed and validated from the perspective of the Japanese healthcare system and cultural backgrounds. This scale may be useful for developing assessments and interventions to improve patient satisfaction with ER nursing.

Introduction: Burnout among healthcare professionals in intensive care units (ICUs) is a serious issue that leads to early retirement and medication errors. Their gender, lower years of experience, and lower education have been reported as risk factors. Simultaneously, mutual support-commonly referred to as "back-up behavior," in which staff members support each other-is critical for team performance. However, little is known about the influence of mutual support among ICU healthcare professionals on burnout. The U.S. Agency for Healthcare Research and Quality refers to mutual support as the involvement of team members in: assisting one another, providing and receiving feedback, and exerting assertive and advocacy behaviors when patient safety is threatened., Objective: This study aimed to verify the hypothesis that lower mutual support among ICU healthcare professionals is associated with increased probability of burnout., Methods: A web-based survey was conducted from March 4 to 20, 2021. All ICU healthcare professionals in Japan were included. An invitation was sent via the mailing list of the Japanese Society of Intensive Care Medicine and asked to mail to local communities and social network services. We measured burnout severity using the Maslach Burnout-Human Services Survey and mutual support using the TeamSTEPPS Teamwork Perceptions Questionnaire, as well as occupational background. The cutoff value for burnout was predefined and conducted logistic regression., Results: We received 335 responses, all of which were analyzed. The majority of respondents were nurses (58.5%), followed by physicians (18.5%) and clinical engineers (10.1%). The burnout group scored significantly lower on mutual support than the non-burnout group. After adjusting for covariates in a logistic regression, low mutual support was an independent factor predicting a high probability of burnout., Conclusions: This study suggests that it is important to focus on mutual support among ICU healthcare professionals to reduce the frequency of burnout., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Background: Extubation failure, i.e., reintubation in ventilated patients, is a well-known risk factor for mortality and prolonged stay in the intensive care unit (ICU). Although sputum volume is a risk factor, the frequency of tracheal suctioning has not been validated as a predictor of reintubation. We conducted this study to examine whether frequent tracheal suctioning is a risk factor for reintubation., Patients and Methods: We included adult patients who were intubated for > 72 h in the ICU and extubated after completion of spontaneous breathing trial (SBT). We compared the characteristics and weaning-related variables, including the frequency of tracheal suctioning between patients who required reintubation within 24 h after extubation and those who did not, and examined the factors responsible for reintubation., Results: Of the 400 patients enrolled, reintubation was required in 51 (12.8%). The most common cause of reintubation was difficulty in sputum excretion (66.7%). There were significant differences in sex, proportion of patients with chronic kidney disease, pneumonia, ICU admission type, the length of mechanical ventilation, and ICU stay between patients requiring reintubation and those who did not. Multivariate analysis showed frequent tracheal suction (> once every 2 h) and the length of mechanical ventilation were independent factors for predicting reintubation., Conclusion: We should examine the frequency of tracheal suctioning > once every 2 h in addition to the length of mechanical ventilation before deciding to extubate after completion of SBT in patients intubated for > 72 h in the ICU., (© 2022. The Author(s).)

Introduction: The medical emergency team enables the limitation of patients' progression to critical illness in the general ward. The early warning scoring system (EWS) is one of the criteria for medical emergency team activation; however, it is not a valid criterion to predict the prognosis of patients with MET activation., Aim: In this study, the National Early Warning Score (NEWS) and Rapid Emergency Medicine Score (REMS) was compared with that of the Acute Physiology and Chronic Health Evaluation II (APACHE II) score in predicting the prognosis of patients who had been treated a medical emergency team., Material and Methods: In this single-centre retrospective cohort study, patients treated by a medical emergency team between April 2013 and March 2019 and the 28-day prognosis of MET-activated patients were assessed using APACHE II, NEWS, and REMS., Results: Of the 196 patients enrolled, 152 (77.5%) were men, and 44 (22.5%) were women. Their median age was 68 years (interquartile range: 57-76 years). The most common cause of medical emergency team activation was respiratory failure (43.4%). Univariate analysis showed that APACHE II score, NEWS, and REMS were associated with 28-day prognostic mortality. There was no significant difference in the area under the receiver operating characteristic curve of APACHE II (0.76), NEWS (0.67), and REMS (0.70); however, the sensitivity of NEWS (0.70) was superior to that of REMS (0.47)., Conclusion: NEWS is a more sensitive screening tool like APACHE II than REMS for predicting the prognosis of patients with medical emergency team activation. However, because the accuracy of NEWS was not sufficient compared with that of APACHE II score, it is necessary to develop a screening tool with higher sensitivity and accuracy that can be easily calculated at the bedside in the general ward., Competing Interests: Conflict of interest The authors declare no conflict of interest., (© 2021 Junpei Haruna, Hiroomi Tatsumi, Satoshi Kazuma, Hiromitsu Kuroda, Yuya Goto, Wakiko Aisaka, Hirofumi Terada, Tomoko Sonoda, Yoshiki Masuda, published by Sciendo.)

Visitation restrictions for family members are problematic in intensive care management due to the COVID-19 pandemic. We analyzed the usefulness of an intensive care unit (ICU) diary about the experiences of family members of critical COVID-19 patients. Four family members of 2 COVID-19 patients participated in this report. Both patients were transferred to our ICU after 2 weeks of treatment at another ICU. An ICU diary was given to their family members post-transfer. The family members were interviewed before and after the patients' discharge; the recorded interviews were analyzed and categorized into several clusters using a text mining method. Five categories regarding their anxious feelings were classified before the use of the ICU diary, and 3 categories were based on their positive feelings after the use of the ICU diary. Intensive care unit diaries may be beneficial for disclosing patients' information when visitation restrictions are exercised due to the COVID-19 pandemic., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

There are many outstanding questions about how to control the global COVID-19 pandemic. The information void has been especially stark in the World Health Organization Africa Region, which has low per capita reported cases, low testing rates, low access to therapeutic drugs, and has the longest wait for vaccines. As with all disease, the central challenge in responding to COVID-19 is that it requires integrating complex health systems that incorporate prevention, testing, front line health care, and reliable data to inform policies and their implementation within a relevant timeframe. It requires that the population can rely on the health system, and decision-makers can rely on the data. To understand the process and challenges of such an integrated response in an under-resourced rural African setting, we present the COVID-19 strategy in Ifanadiana District, where a partnership between Malagasy Ministry of Public Health (MoPH) and non-governmental organizations integrates prevention, diagnosis, surveillance, and treatment, in the context of a model health system. These efforts touch every level of the health system in the district-community, primary care centers, hospital-including the establishment of the only RT-PCR lab for SARS-CoV-2 testing outside of the capital. Starting in March of 2021, a second wave of COVID-19 occurred in Madagascar, but there remain fewer cases in Ifanadiana than for many other diseases (e.g., malaria). At the Ifanadiana District Hospital, there have been two deaths that are officially attributed to COVID-19. Here, we describe the main components and challenges of this integrated response, the broad epidemiological contours of the epidemic, and how complex data sources can be developed to address many questions of COVID-19 science. Because of data limitations, it still remains unclear how this epidemic will affect rural areas of Madagascar and other developing countries where health system utilization is relatively low and there is limited capacity to diagnose and treat COVID-19 patients. Widespread population based seroprevalence studies are being implemented in Ifanadiana to inform the COVID-19 response strategy as health systems must simultaneously manage perennial and endemic disease threats., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer SN declared a shared affiliation, with no collaboration, with one of the authors AG, to the handling editor at the time of the review., (Copyright © 2021 Rakotonanahary, Andriambolamanana, Razafinjato, Raza-Fanomezanjanahary, Ramanandraitsiory, Ralaivavikoa, Tsirinomen'ny Aina, Rahajatiana, Rakotonirina, Haruna, Cordier, Murray, Cowley, Jordan, Krasnow, Wright, Gillespie, Docherty, Loyd, Evans, Drake, Ngonghala, Rich, Popper, Miller, Ihantamalala, Randrianambinina, Ramiandrisoa, Rakotozafy, Rasolofomanana, Rakotozafy, Andriamahatana Vololoniaina, Andriamihaja, Garchitorena, Rakotonirina, Mayfield, Finnegan and Bonds.)

Few studies have examined the epidemiology of post-intensive care syndrome in Japan. This study investigated the mental health and quality of life of patients living at home in Japan after intensive care unit (ICU) discharge. Additionally, we examined whether unplanned admission to the ICU was associated with more severe post-traumatic stress disorder (PTSD), anxiety, and depressive symptoms. An ambidirectional cohort study was conducted at 12 ICUs in Japan. Patients who stayed in the ICU for > 3 nights and were living at home for 1 year afterward were included. One year after ICU discharge, we retrospectively screened patients and performed a mail survey on a monthly basis, including the Impact of Event Scale-Revised (IER-S), the Hospital Anxiety Depression Scale (HADS), and the EuroQOL-5 Dimension (EQ-5D-L) questionnaires. Patients' characteristics, delirium and coma status, drugs used, and ICU and hospital length of stay were assessed from medical records. Descriptive statistics and multilevel linear regression modeling were used to examine our hypothesis. Among 7,030 discharged patients, 854 patients were surveyed by mail. Of these, 778 patients responded (response rate = 91.1%). The data from 754 patients were analyzed. The median IES-R score was 3 (interquartile range [IQR] = 1‒9), and the prevalence of suspected PTSD was 6.0%. The median HADS anxiety score was 4.00 (IQR = 1.17‒6.00), and the prevalence of anxiety was 16.6%. The median HADS depression score was 5 (IQR = 2‒8), and the prevalence of depression was 28.1%. EQ-5D-L scores were lower in our participants than in the sex- and age-matched Japanese population. Unplanned admission was an independent risk factor for more severe PTSD, anxiety, and depressive symptoms. Approximately one-third of patients in the general ICU population experienced mental health issues one year after ICU discharge. Unplanned admission was an independent predictor for more severe PTSD symptoms., Competing Interests: The authors have declared that no competing interests exist.

Precision health mapping is a technique that uses spatial relationships between socio-ecological variables and disease to map the spatial distribution of disease, particularly for diseases with strong environmental signatures, such as diarrhoeal disease (DD). While some studies use GPS-tagged location data, other precision health mapping efforts rely heavily on data collected at coarse-spatial scales and may not produce operationally relevant predictions at fine enough spatio-temporal scales to inform local health programmes. We use two fine-scale health datasets collected in a rural district of Madagascar to identify socio-ecological covariates associated with childhood DD. We constructed generalized linear mixed models including socio-demographic, climatic and landcover variables and estimated variable importance via multi-model inference. We find that socio-demographic variables, and not environmental variables, are strong predictors of the spatial distribution of disease risk at both individual and commune-level (cluster of villages) spatial scales. Climatic variables predicted strong seasonality in DD, with the highest incidence in colder, drier months, but did not explain spatial patterns. Interestingly, the occurrence of a national holiday was highly predictive of increased DD incidence, highlighting the need for including cultural factors in modelling efforts. Our findings suggest that precision health mapping efforts that do not include socio-demographic covariates may have reduced explanatory power at the local scale. More research is needed to better define the set of conditions under which the application of precision health mapping can be operationally useful to local public health professionals.

Introduction: Despite renewed commitment to universal health coverage and health system strengthening (HSS) to improve access to primary care, there is insufficient evidence to guide their design and implementation. To address this, we conducted an impact evaluation of an ongoing HSS initiative in rural Madagascar, combining data from a longitudinal cohort and primary health centres., Methods: We carried out a district representative household survey at the start of the HSS intervention in 2014 in over 1500 households in Ifanadiana district, and conducted follow-up surveys at 2 and 4 years. At each time point, we estimated maternal, newborn and child health coverage; economic and geographical inequalities in coverage; and child mortality rates; both in the HSS intervention and control catchments. We used logistic regression models to evaluate changes associated with exposure to the HSS intervention. We also estimated changes in health centre per capita utilisation during 2013 to 2018., Results: Child mortality rates decreased faster in the HSS than in the control catchment. We observed significant improvements in care seeking for children under 5 years of age (OR 1.23; 95% CI 1.05 to 1.44) and individuals of all ages (OR 1.37, 95% CI 1.19 to 1.58), but no significant differences in maternal care coverage. Economic inequalities in most coverage indicators were reduced, while geographical inequalities worsened in nearly half of the indicators., Conclusion: The results demonstrate improvements in care seeking and economic inequalities linked to the early stages of a HSS intervention in rural Madagascar. Additional improvements in this context of persistent geographical inequalities will require a stronger focus on community health., Competing Interests: Competing interests: Some authors are current or former employees of institutions discussed in this article, including the non-governmental organisation PIVOT and the Government of Madagascar. These affiliations are explicitly listed in the article., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Pigs are considered one of the relevant animal models for ocular research as they share several histological and anatomical similarities with the human eye. With the increasing interest in juvenile animal models, this study aimed to describe the postnatal development of ocular structures in 16 Göttingen minipigs and 25 F2 domestic pigs, between birth and 6 months of age, using histopathology and immunohistochemistry against Ki-67, caspase-3, calbindin, glial fibrillary acidic protein, rhodopsin, and synaptophysin. All ocular structures in both pig breeds were incompletely developed at birth and for variable periods postnatally. Noteworthy histological features of immaturity included vascularization in the corneal stroma in neonatal Göttingen minipigs, increased cellularity in different substructures, remnants of the hyaloid vasculature, short and poorly ramified ciliary body processes, and a poorly developed cone inner segment. Increased cellular proliferation, highlighted by abundant Ki-67 immunolabeling, was observed in almost all developing structures of the pig eye for variable periods postnatally. Apoptosis, highlighted with caspase-3 immunolabeling, was observed in the retinal inner nuclear layer at birth and in the regressing hyaloid vasculature remnants. Immunohistochemistry against rhodopsin, synaptophysin, and calbindin demonstrated the short size of the developing photoreceptors and the immature cone inner segment morphology. Calbindin labeling revealed significant differences in the amount of positively labeled cone nuclei between the retinal area centralis and the non-area centralis regions. The elongation of Müller cell processes in the developing retina was shown with glial fibrillary acidic protein. In both pig breeds, the eyes reached histomorphological and immunohistochemical maturity at 6 months of age.

Health care is most effective when a patient's basic primary care needs are met as close to home as possible, with advanced care accessible when needed. In Ifanadiana District, Madagascar, a collaboration between the Ministry of Public Health (MoPH) and PIVOT, a non-governmental organization (NGO), fosters Networks of Care (NOC) to support high-quality, patient-centered care. The district's health system has three levels of care: community, health center, district hospital; a regional hospital is available for tertiary care services. We explore the MoPH/PIVOT collaboration through a case study which focuses on noteworthy elements of the collaboration across the four NOC domains: (I) agreement and enabling environment, (II) operational standards, (III) quality, efficiency, and responsibility, (IV) learning and adaptation. Under Domain I, we describe formal agreements between the MoPH and PIVOT and the process for engaging communities in creating effective NOC. Domain II discusses patient referral across levels of the health system and improvements to facility readiness and service availability. Under Domain III the collaboration prioritizes communication and supervision to support clinical quality, and social support for patients. Domain IV focuses on evaluation, research, and the use of data to modify programs to better meet community needs. The case study, organized by the domains of the NOC framework, demonstrates that a collaboration between the MoPH and an NGO can create effective NOC in a remote district with limited accessibility and advance the country's agenda to achieve universal health coverage.

Background: In order to reach the health-related Sustainable Development Goals (SDGs) by 2030, gains attained in access to primary healthcare must be matched by gains in the quality of services delivered. Despite the broad consensus around the need to address quality, studies on the impact of health system strengthening (HSS) have focused predominantly on measures of healthcare access. Here, we examine changes in the content of maternal and child care as a proxy for healthcare quality, to better evaluate the effectiveness of an HSS intervention in a rural district of Madagascar. The intervention aimed at improving system readiness at all levels of care (community health, primary health centers, district hospital) through facility renovations, staffing, equipment, and training, while removing logistical and financial barriers to medical care (e.g., ambulance network and user-fee exemptions)., Methods and Findings: We carried out a district-representative open longitudinal cohort study, with surveys administered to 1,522 households in the Ifanadiana district of Madagascar at the start of the HSS intervention in 2014, and again to 1,514 households in 2016. We examined changes in healthcare seeking behavior and outputs for sick-child care among children <5 years old, as well as for antenatal care and perinatal care among women aged 15-49. We used a difference-in-differences (DiD) analysis to compare trends between the intervention group (i.e., people living inside the HSS catchment area) and the non-intervention comparison group (i.e., the rest of the district). In addition, we used health facility-based surveys, monitoring service availability and readiness, to assess changes in the operational capacities of facilities supported by the intervention. The cohort study included 657 and 411 children (mean age = 2 years) reported to be ill in the 2014 and 2016 surveys, respectively (27.8% and 23.8% in the intervention group for each survey), as well as 552 and 524 women (mean age = 28 years) reported to have a live birth within the previous two years in the 2014 and 2016 surveys, respectively (31.5% and 29.6% in the intervention group for each survey). Over the two-year study period, the proportion of people who reported seeking care at health facilities experienced a relative change of +51.2% (from 41.4% in 2014 to 62.5% in 2016) and -7.1% (from 30.0% to 27.9%) in the intervention and non-intervention groups, respectively, for sick-child care (DiD p-value = 0.01); +11.4% (from 78.3% to 87.2%), and +10.3% (from 67.3% to 74.2%) for antenatal care (p-value = 0.75); and +66.2% (from 23.1% to 38.3%) and +28.9% (from 13.9% to 17.9%) for perinatal care (p-value = 0.13). Most indicators of care content, including rates of medication prescription and diagnostic test administration, appeared to increase more in the intervention compared to in the non-intervention group for the three areas of care we assessed. The reported prescription rate for oral rehydration therapy among children with diarrhea changed by +68.5% (from 29.6% to 49.9%) and -23.2% (from 17.8% to 13.7%) in the intervention and non-intervention groups, respectively (p-value = 0.05). However, trends observed in the care content varied widely by indicator and did not always match the large apparent increases observed in care seeking behavior, particularly for antenatal care, reflecting important gaps in the provision of essential health services for individuals who sought care. The main limitation of this study is that the intervention catchment was not randomly allocated, and some demographic indicators were better for this group at baseline than for the rest of the district, which could have impacted the trends observed., Conclusion: Using a district-representative longitudinal cohort to assess the content of care delivered to the population, we found a substantial increase over the two-year study period in the prescription rate for ill children and in all World Health Organization (WHO)-recommended perinatal care outputs assessed in the intervention group, with more modest changes observed in the non-intervention group. Despite improvements associated with the HSS intervention, this study highlights the need for further quality improvement in certain areas of the district's healthcare system. We show how content of care, measured through standard population-based surveys, can be used as a component of HSS impact evaluations, enabling healthcare leaders to track progress as well as identify and address specific gaps in the provision of services that extend beyond care access., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: some authors are current or former employees of institutions discussed in this article, including the nongovernmental organization PIVOT and the Government of Madagascar. MHB is cofounder and scientific director of PIVOT; ACM is senior research advisor of PIVOT; LFC is monitoring and evaluation coordinator of PIVOT; JH is medical programs coordinator of PIVOT; DM is former medical point of contact of PIVOT; MR and H-TRR are, respectively, head of and data analyst for the Demography and Social Statistics unit at the National Institute of Statistics of Madagascar; MAO is former country director of PIVOT, BRR is monitoring and evaluation manager of PIVOT; MM is a member of the Editorial Board of PLOS Medicine; and AG is research adviser of PIVOT.

Introduction: The Sustainable Development Goals framed an unprecedented commitment to achieve global convergence in child and maternal mortality rates through 2030. To meet those targets, essential health services must be scaled via integration with strengthened health systems. This is especially urgent in Madagascar, the country with the lowest level of financing for health in the world. Here, we present an interim evaluation of the first 2 years of a district-level health system strengthening (HSS) initiative in rural Madagascar, using estimates of intervention coverage and mortality rates from a district-wide longitudinal cohort., Methods: We carried out a district representative household survey at baseline of the HSS intervention in over 1500 households in Ifanadiana district. The first follow-up was after the first 2 years of the initiative. For each survey, we estimated maternal, newborn and child health (MNCH) coverage, healthcare inequalities and child mortality rates both in the initial intervention catchment area and in the rest of the district. We evaluated changes between the two areas through difference-in-differences analyses. We estimated annual changes in health centre per capita utilisation from 2013 to 2016., Results: The intervention was associated with 19.1% and 36.4% decreases in under-five and neonatal mortality, respectively, although these were not statistically significant. The composite coverage index (a summary measure of MNCH coverage) increased by 30.1%, with a notable 63% increase in deliveries in health facilities. Improvements in coverage were substantially larger in the HSS catchment area and led to an overall reduction in healthcare inequalities. Health centre utilisation rates in the catchment tripled for most types of care during the study period., Conclusion: At the earliest stages of an HSS intervention, the rapid improvements observed for Ifanadiana add to preliminary evidence supporting the untapped and poorly understood potential of integrated HSS interventions on population health., Competing Interests: Competing interests: Some authors are current or former employees of institutions discussed in this article, including the non-governmental organisation PIVOT and the Government of Madagascar. These affiliations are explicitly listed in the article.

As in many altricial species, rats are born with fused eyelids and markedly underdeveloped eyes. While the normal histology of the eyes of mature rats is known, the histomorphological changes occurring during postnatal eye development in this species remain incompletely characterized. This study was conducted to describe the postnatal development of ocular structures in Sprague-Dawley (SD) rats during the first month of age using histology and immunohistochemistry (IHC). Both eyes were collected from 51 SD rats at 13 time points between postnatal day (PND)1 and PND30. Histologic examination of hematoxylin and eosin-stained sections was performed, as well as IHC for cleaved-caspase-3 and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) to evaluate apoptosis, and IHC for Ki-67 and phospho-histone-H3 to evaluate cell proliferation. Extensive ocular tissue remodeling occurred prior to the eyelid opening around PND14 and reflected the interplay between apoptosis and cell proliferation. Apoptosis was particularly remarkable in the maturing subcapsular anterior epithelium of the lens, the inner nuclear and ganglion cell layers of the developing retina, and the Harderian gland, and was involved in the regression of the hyaloid vasculature. Nuclear degradation in the newly formed secondary lens fibers was noteworthy after birth and was associated with TUNEL-positive nuclear remnants lining the lens organelle-free zone. Cell proliferation was marked in the developing retina, cornea, iris, ciliary body and Harderian gland. The rat eye reached histomorphological maturity at PND21 after a rapid phase of morphological changes characterized by the coexistence of cell death and proliferation.

Histological examination of the rat placenta and fetus is uncommon. Toxicological studies mainly rely on gross examination of the fetus and on fetal and placental weights. These are often insufficient to assess the fetal and placental toxicity of xenobiotics. The small size of the fetus makes its dissection labor-intensive. Thus, our objective was to develop a simple and accurate technique to evaluate the rat fetus and placenta. Sprague-Dawley rat fetuses at gestational day 19.5 ( n = 18) and their placentas ( n = 32) were fixed in formalin. Placentas were cut transversally in the center. Fetuses were cut following a freehand whole-body serial sectioning diagram adapted from Wilson's method. Sections were stained with hematoxylin-eosin-phloxine-saffron, and histomorphometry was used to measure the area of the fetal placental region (27.2 ± 1.7 mm 2 ), including the labyrinth (22.2 ± 1.0 mm 2 ) and the basal zone (4.8 ± 0.8 mm 2 ). Our whole-fetus serial sectioning technique resulted in 12 precise cutting planes that fit on 3 histological slides, enabling the examination of most organs without labor-intensive dissection. Quantitative analysis of placental areas improves the understanding of the pathogenesis of treatment-related changes. This technique provides a standardized method for future research in pertinent fields such as developmental biology and toxicology.

Both a rodent and a nonrodent species are required for evaluation in nonclinical safety studies conducted to support human clinical trials. Historically, dogs and nonhuman primates have been the nonrodent species of choice. Swine, especially the miniature swine or minipigs, are increasingly being used in preclinical safety as an alternate nonrodent species. The pig is an appropriate option for these toxicology studies based on metabolic pathways utilized in xenobiotic biotransformation. Both similarities and differences exist in phase I and phase II biotransformation pathways between humans and pigs. There are numerous breeds of pigs, yet only a few of these breeds are characterized with regard to both xenobiotic-metabolizing enzymes and background pathology findings. Some specific differences in these enzymes based on breed and sex are known. Although swine have been used extensively in biomedical research, there is also a paucity of information in the current literature detailing the incidence of background lesions and differences between commonly used breeds. Here, the xenobiotic-metabolizing enzymes are compared between humans and pigs, and minipig background pathology changes are reviewed with emphasis on breed differences., (© The Author(s) 2016.)

Swine, especially the miniature swine or minipigs, are increasingly being used in preclinical safety assessment of small molecules, biopharmaceutical agents, and medical devices as an alternate nonrodent species. Although swine have been used extensively in biomedical research, there is a paucity of information in the current literature detailing the incidence of background lesions and differences in incidence between commonly used breeds. This article is a collaborative effort between multiple organizations to define and document lesions found in the common breeds of minipigs used for toxicological risk assessment in North America (NA) and the European Union (EU). We retrospectively assessed 10 years of historical control data from several institutions located in NA and EU, covering the period of 2004-2015. Here we report the background lesions with consideration of breed and geographical location. To our knowledge, this is the first report documenting spontaneous background lesions in commonly used breeds of swine in both NA and EU. This report serves as a resource to pathologists and will aid in interpretation of findings and differentiation of background from test article-related changes., (© The Author(s) 2015.)

Healthy ruminants carry intestinal Shiga toxin (Stx)-producing Escherichia coli (STEC). Stx has antiviral activities in vitro and STEC numbers correlate with reduced early viremia in sheep experimentally infected with bovine leukemia virus (BLV). This study assessed the impact of intestinal STEC on BLV-induced disease for one year post-BLV-challenge. High STEC scores (CFU/g feces x frequency of STEC-positive samples) correlated with good health, whereas poor weight gain, distress, and tumor development occurred only among animals with low STEC scores. STEC carriage was associated with increased percentages of B cells in peripheral blood.

Bovine viral diarrhea (BVD) viruses are pestiviruses that have been isolated from domestic and wild ruminants. There is serologic evidence of pestiviral infection in more than 40 species of free-range and captive mammals. Vertical transmission can produce persistently infected animals that are immunotolerant to the infecting strain of Bovine viral diarrhea virus (BVDV) and shed virus throughout their lives. Seven species (white-tailed deer, mouse deer, eland, domestic cattle, alpaca, sheep, and pigs) have been definitively identified as persistently infected with BVDV. This study provides serological, molecular, immunohistochemical, and histological evidence for BVDV infection in 2 captive mountain goats from a zoological park in Idaho. The study was triggered by isolation of BVDV from tissues and immunohistochemical identification of viral antigen within lesions of a 7-month-old male mountain goat (goat 1). Blood was collected from other mountain goats and white-tailed and mule deer on the premises for BVDV serum neutralization, viral isolation, and reverse transcription polymerase chain reaction. One 3-month-old mountain goat (goat 2) was antibody negative and BVDV positive in serum samples collected 3 months apart. This goat subsequently died, and though still antibody negative, BVDV was isolated from tissues and identified by immunohistochemistry within lesions. Sequencing and phylogenetic analysis identified the isolates as BVDV-2. These findings provide evidence of persistent infection in a mountain goat, underscoring the need for pestivirus control strategies for wild ruminants in zoological collections.

We evaluated the effects of immunostimulation in the development of postweaning multisystemic wasting syndrome (PMWS) in 930 pigs 53 to 54 d old in a grower/finisher barn with a history of PMWS. The pigs were allocated to 5 treatment groups: 4 groups received a single intramuscular injection of RespiSure-ONE (a commercial Mycoplasma hyopneumoniae vaccine; n = 197), Emulsigen (an oil-based adjuvant; n = 172), Alhydrogel (an aluminum-hydroxide-based adjuvant; n = 172), or physiologic saline (n = 218); 1 group received no treatment (n = 171). Pigs affected by PMWS were found in all the groups. Antigen to Porcine circovirus type 2 (PCV-2) was detected by immunohistochemical testing within lesions of mesenteric lymph node, spleen, Peyer's patch, and lung of affected pigs. There was no significant difference in the incidence of PMWS among the groups. The findings indicate that immunostimulation did not influence the expression of PMWS in this study. Thus, routine vaccination against swine diseases may not significantly contribute to the occurrence of PMWS under field conditions.

Unlabelled: Because individual variation is a likely factor affecting both the incidence and severity of side effects and the analgesic efficacy of epidural opioids, assessment of individual variation could be useful in deciding optimal dosage. By evaluating the response to a small test dose of IV fentanyl, we designed this study to predict the degree of pain relief and the incidence of side effects in patients who would be receiving postoperative epidural fentanyl. Before the induction of anesthesia, 50 micro g of fentanyl was administered IV, and 2 min after fentanyl, the patient response was evaluated. Twenty-three patients, who reported nausea, sleepiness, dizziness, sensation of warmth, and other symptoms, were categorized as responders (Group R); the remaining 20 patients were categorized as nonresponders (Group NR). At the completion of surgery, infusion of epidural fentanyl was administered (0.3 mg/d in 0.25% bupivacaine) for 96 h. At postoperative Hours 6 and 24, Group R had significantly lower visual analog scale scores for postoperative pain intensity and required fewer analgesics than Group NR. The incidence of side effects, however, was 74% for Group R and 10% for Group NR (P < 0.05), and side effects were more serious in Group R. This study demonstrates that preoperative administration of a small dose of fentanyl during the induction of anesthesia enables prediction of the analgesic efficacy of postoperative epidural fentanyl and the incidence and severity of side effects., Implications: Preoperative administration of a small dose of fentanyl during the induction of anesthesia enables prediction of the analgesic efficacy of postoperative epidural fentanyl and the incidence and severity of side effects.